The purpose of the proposed research is to characterize and isolate a growth factor derived from cultured fetal rat calvaria which stimulates bone DNA and collagen synthesis in vitro. During the past six years, I have examined the effects of known hormones and growth factors on aspects of bone formation by studying their effects on DNA, RNA, and collagen and noncollagen protein synthesis in cultures of 21-day fetal rat calvaria. Insulin and the somatomedins were found to have a direct stimulatory effect on bone collagen synthesis. However, the hormonal control of bone formation has not yet been fully elucidated, particularly since recent studies from this laboratory have indicated the existence of a growth factor derived from cultured calvaria. This suggests that local factors as well as systemic factors and hormones are important in the control of bone growth. Furthermore, the stimulatory effect of the bone-derived growth factor on bone collagen synthesis is cortisol dependent indicating that local factors interact with systemic hormones. In the present proposal, I plan to use an organ culture system to examine effects on nucleic acid, bone collagen and noncollagen protein synthesis and other parameters of bone formation. Using these methods, I will attempt to characterize the biological properties of the growth factor present in conditioned medium from cultured calvaria. In addition, experiments to determine the chemical properties and to isolate the factor will be performed. This will be attempted by the use of various chromatographic and electrophoretic techniques available in my laboratory. These investigations should provide valuable new information about the physiologic regulation of bone formation by local factors and their relationship to systemic hormones.